Diseases of the eye

Nesterova, Anastasia P.; Klimov, Eugene; Zharkova, Maria; Sozin, Sergey; Соболев, В. В.; Ivanikova, Natalia V.; Shkrob, Maria; Yuryev, Anton

doi:10.1016/b978-0-12-817086-1.00006-3

Cited by 2 publications

(2 citation statements)

References 51 publications

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“…Shown in Supplementary Table 8, Figure 2e and Supplementary Figure 4, pathway enrichment using the 22 genes mapped from the 22 SNPs was performed with Enrichr (Kuleshov et al 2016) and as expected, found neural and microtubule structural related pathway hits from Reactome (Fabregat et al 2018) and Elsevier pathway (Nesterova et al 2019) database resources. The top pathways were Synaptic Exocytosis in Dementia (MAPT and NSF, p-value 0.00026), Genes with Mutations Associated with Frontotemporal Dementia (MAPT, p-value 0.006) and Hypoxia related pathways (BNIP3, p-value 0.024).…”

Section: Gwas Summary Statisticssupporting

confidence: 53%

Exploring autism and autism co-occurring condition associations to elucidate multivariate genetic mechanisms and insights

Salenius,

Väljä,

Thusberg

et al. 2024

Preprint

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BackgroundGenome-wide association (GWAS) and large scaled exome based studies have successfully uncovered hundreds of associations and genes related to autism. Autism is a partially heritable neurodevelopmental condition. Autistic people may also have other co-occurring conditions such as ADHD, anxiety disorders, depression, mental health issues, learning difficulty, physical health conditions and communication challenges. The concomitant development of autism and other neurological conditions is assumed to result from a complex interplay between genetics and the environment. However, only a limited number of studies have performed multivariate genetic autism association studies.MethodsWe conducted the largest multivariate GWAS with autism and 11 autism co-occurring traits (ADHD, ADHD child, anxiety, IBS, depression, digestion disorders, education attainment, epilepsy, panic, social phobia) using summary statistics from leading reputable consortiums: iPSYCH, PGC, 23andMe and UK Biobank. Multivariate associations and central traits were further identified. Subsequently, colocalization and Mendelian randomization (MR) analysis were performed on the associations identified with the central traits containing autism. To further validate our findings we utilized independent datasets consisting of 35,584 exome sequence iPSYCH data and 53 (13 probands) Whole Genome Sequence from the GEMMA project.ResultsMultivariate GWAS resulted in 380 significant associations (p-value < 5e-8), among which 203 are reported for the first time for any trait. 22 SNPs were identified to contain autism and one or more comorbidities in their central trait set, including variants mapped to known SFARI autism genes such as MAPT and NEGR1. NSF, a serotonin receptor binding gene, was found to be associated with autism with education attainment. Mendelian randomization and colocalization analyses found that education attainment, ADHD and ADHD childhood are liable traits toward autism. Additionally, allele proportions and distribution differences between MAPT (17q21.31) region aberrations and MAPT H1/H2 haplotypes, known to associate with neurodevelopment, and the reported autism-central SNPs were found within GEMMA autism probands and controls. Pathway and gene card analysis also implicated microbiome, enteric inflammation, and central nervous system enrichments.ConclusionsOur study combined multivariate genome-wide association testing with systematic decomposition to identify novel genetic associations related to autism and autism co-occurring driver traits. Statistical tests were applied to discern evidence for shared and interpretable liability between autism and co-occurring traits. We additionally detected differences in the SNP association frequency patterns between autism probands and familial controls in an independent validation cohort. These findings contribute to our understanding of the complex genetic underpinnings of autism and provide valuable insights into its potential driver traits and genetic markers.

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Section: Gwas Summary Statisticssupporting

confidence: 53%

Exploring autism and autism co-occurring condition associations to elucidate multivariate genetic mechanisms and insights

Salenius,

Väljä,

Thusberg

et al. 2024

Preprint

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“…Moreover, AH provides nutrients and oxygen to and removes metabolic waste from avascular ocular tissues such as the cornea, lens, and trabecular meshwork [ 1 , 5 , 6 ]. It is similar to blood plasma in composition, though has a lower abundance of protein and glucose [ 7 ]. The protein component of AH includes mostly albumin with a small fraction of growth factors, and cytokines [ 8 ].…”

Section: Aqueous Humourmentioning

confidence: 99%

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

Uddin

Rutar

2022

IJMS

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Clearance of ocular fluid and metabolic waste is a critical function of the eye in health and disease. The eye has distinct fluid outflow pathways in both the anterior and posterior segments. Although the anterior outflow pathway is well characterized, little is known about posterior outflow routes. Recent studies suggest that lymphatic and glymphatic systems play an important role in the clearance of fluid and waste products from the posterior segment of the eye. The lymphatic system is a vascular network that runs parallel to the blood circulatory system. It plays an essential role in maintenance of fluid homeostasis and immune surveillance in the body. Recent studies have reported lymphatics in the cornea (under pathological conditions), ciliary body, choroid, and optic nerve meninges. The evidence of lymphatics in optic nerve meninges is, however, limited. An alternative lymphatic system termed the glymphatic system was recently discovered in the rodent eye and brain. This system is a glial cell-based perivascular network responsible for the clearance of interstitial fluid and metabolic waste. In this review, we will discuss our current knowledge of ocular lymphatic and glymphatic systems and their role in retinal degenerative diseases.

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Diseases of the eye

Cited by 2 publications

References 51 publications

Exploring autism and autism co-occurring condition associations to elucidate multivariate genetic mechanisms and insights

Exploring autism and autism co-occurring condition associations to elucidate multivariate genetic mechanisms and insights

Ocular Lymphatic and Glymphatic Systems: Implications for Retinal Health and Disease

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